ARTEMIS Load: Optimal Timing of Dronedarone Initiation After Conversion in Patients With Persistent Atrial Fibrillation

Sponsor

Sanofi (Industry)

Overall Status

Completed

CT.gov ID

NCT01140581

Collaborator

(none)

402

Enrollment

111

Locations

Arms

Duration (Months)

3.6

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Primary Objective:

Evaluate the rate of Atrial Fibrillation (AF) recurrences one month after randomization according to different timings of initiation of dronedarone.

Secondary Objective:

Evaluate the rate of AF recurrences two months after randomization.
Assess the safety of the change from amiodarone to dronedarone
Assess dronedarone safety
Explore dronedarone and its active metabolite plasma level (in a subset of countries)
Explore potential Pharmacokinetic (PK) interaction between dronedarone and amiodarone (in a subset of countries)

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation	Drug: DRONEDARONE	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

402 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized, International, Multi-center, Open-label Study to Document Optimal Timing of Initiation of Dronedarone Treatment After Conversion With Loading Dose of Amiodarone in Patients With Persistent Atrial Fibrillation Requiring Conversion of AF.

Study Start Date :

Sep 1, 2010

Actual Primary Completion Date :

Dec 1, 2011

Actual Study Completion Date :

Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group A Amiodarone 600 mg daily for 1 week then 400 mg daily for 1 week then 200 mg daily for 2 weeks followed by dronedarone 400 mg twice daily for 8 weeks	Drug: DRONEDARONE Pharmaceutical form: tablet Route of administration: oral Dose regimen: 400 mg
Experimental: Group B Amiodarone 600 mg daily for 1 week then 400 mg daily for 1 week then 200 mg daily for 2 weeks. Two weeks wash-out followed by dronedarone 400 mg twice daily for 6 weeks	Drug: DRONEDARONE Pharmaceutical form: tablet Route of administration: oral Dose regimen: 400 mg
Experimental: Group C Amiodarone 600 mg daily for 1 week then 400 mg daily for 1 week then 200 mg daily for 2 weeks. Four weeks wash-out followed by dronedarone 400 mg twice daily for 4 weeks	Drug: DRONEDARONE Pharmaceutical form: tablet Route of administration: oral Dose regimen: 400 mg

Arm

Intervention/Treatment

Experimental: Group A

Amiodarone 600 mg daily for 1 week then 400 mg daily for 1 week then 200 mg daily for 2 weeks followed by dronedarone 400 mg twice daily for 8 weeks

Drug: DRONEDARONE

Pharmaceutical form: tablet Route of administration: oral Dose regimen: 400 mg

Experimental: Group B

Amiodarone 600 mg daily for 1 week then 400 mg daily for 1 week then 200 mg daily for 2 weeks. Two weeks wash-out followed by dronedarone 400 mg twice daily for 6 weeks

Drug: DRONEDARONE

Pharmaceutical form: tablet Route of administration: oral Dose regimen: 400 mg

Experimental: Group C

Amiodarone 600 mg daily for 1 week then 400 mg daily for 1 week then 200 mg daily for 2 weeks. Four weeks wash-out followed by dronedarone 400 mg twice daily for 4 weeks

Drug: DRONEDARONE

Pharmaceutical form: tablet Route of administration: oral Dose regimen: 400 mg

Outcome Measures

Primary Outcome Measures

AF recurrences [one month after randomization]
two consecutives 12-lead ECG or Trans-Telephonic ECG monitoring (TTEM) approximatively 10 minutes apart and both showing AF

Secondary Outcome Measures

AF recurrences [two months after randomization]
Symptomatic bradycardia [two months after randomization]
Heart rate at rest < 50 beats per minute
Tachycardia [two months after randomization]
Heart rate at rest > 120 beats per minute
Dronedarone and amiodarone concentrations in plasma [3 hours, 1 week, 2 weeks and 4 weeks after 1st Dronedarone intake]
Limited to a subset of countries

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

Screening:

Persistent AF for more than 72 hours (documented by an ECG taken within the last 72 hours) for whom cardioversion, anti-arrhythmic treatment and anticoagulation treatment are indicated in the opinion of the Investigator
Naive of amiodarone treatment in the last three months
QTc Bazett < 500 ms on 12-lead ECG,
At least one cardiovascular risk factor (i.e. age > 70, hypertension, diabetes, prior cerebrovascular disease or left atrial diameter >= 50 mm

Randomization:

Outpatient and Inpatients (except patients hospitalized during screening period for SAE)
Sinus rhythm
Effective oral anticoagulation verified by International Normalized Ratio/INR (target

QTc Bazett < 500 ms and PR < 280 ms on 12-lead ECG
Completed treatment period with amiodarone (28 days ± 2 days)

Exclusion criteria:

Screening:

Contraindication to oral anticoagulation
Acute condition known to cause AF
Permanent AF
Paroxysmal AF
Bradycardia < 50 bpm on the 12-lead ECG
Clinically overt congestive heart failure:
with New York Heart Association (NYHA) classes III and IV heart failure
with LVEF < 35%
or NYHA class II with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic
or unstable hemodynamic conditions
Severe hepatic impairment
Previous treatment with class I or class III anti-arrhythmic drugs (including sotalol) if taken less than one week
Previous history of amiodarone intolerance or toxicity
Any contraindication as per dronedarone and amiodarone labelling
Wolff-Parkinson-White Syndrome
Previous ablation for atrial fibrillation or any planned ablation in the next 2 months
Contraindicated concomitant treatment:
Potent cytochrome P450 (CYP3A4) inhibitors
Use of drugs or herbal products that prolong the QT interval and known to increase the risk of Torsades de Pointes
Class I or III anti-arrhythmic drugs (including sotalol)

Randomization:

Bradycardia < 50 bpm on the 12-lead ECG
Clinically overt congestive heart failure:
with New York Heart Association (NYHA) classes III and IV heart failure
with LVEF < 35%
or NYHA class II with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic
or unstable hemodynamic conditions
Severe hepatic impairment
Previous treatment with class I or class III anti-arrhythmic drugs (including sotalol) if taken less than one week
Patient in whom the following contraindicated concomitant treatment is mandatory:
Potent cytochrome P450 (CYP3A4) inhibitors
Use of drugs or herbal products that prolong the QT interval and known to increase the risk of Torsades de Pointes
Class I or III anti-arrhythmic drugs (including sotalol)

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Investigational Site Number 009	Adelaide	Australia	5000
2	Investigational Site Number 013	Ballarat	Australia	3350
3	Investigational Site Number 002	Garran	Australia	2605
4	Investigational Site Number 007	Herston	Australia	4006
5	Investigational Site Number 012	Hobart	Australia	7000
6	Investigational Site Number 006	Liverpool	Australia	2170
7	Investigational Site Number 010	Maroubra	Australia	2035
8	Investigational Site Number 001	Nedlands	Australia	6009
9	Investigational Site Number 004	New Lambton	Australia	2305
10	Investigational Site Number 008	Redcliffe	Australia	4020
11	Investigational Site Number 011	South Brisbane	Australia	4101
12	Investigational Site Number 005	Southport	Australia	4215
13	Investigational Site Number 003	Woolloongabba	Australia	4102
14	Investigational Site Number 040-006	Braunau	Austria	5280
15	Investigational Site Number 040-007	Innsbruck	Austria	6020
16	Investigational Site Number 040-002	Linz	Austria	4010
17	Investigational Site Number 040-001	Mödling	Austria	2340
18	Investigational Site Number 040-003	Vienna	Austria
19	Investigational Site Number 040-005	Wien	Austria	1090
20	Investigational Site Number 040-004	Wien	Austria
21	Investigational Site Number 233001	Tallinn	Estonia	10138
22	Investigational Site Number 246-001	Hyvinkää	Finland	05850
23	Investigational Site Number 246-002	Hyvinkää	Finland	05850
24	Investigational Site Number 246-004	Pori	Finland	28210
25	Investigational Site Number 246-003	Seinäjoki	Finland	60220
26	Investigational Site Number 250-006	Avignon Cedex 9	France	84902
27	Investigational Site Number 250-009	BEZIERS Cedex	France	34525
28	Investigational Site Number 250-002	Bron	France	69677
29	Investigational Site Number 250-007	Cholet	France	49300
30	Investigational Site Number 250-008	Lyon Cedex 03	France	69275
31	Investigational Site Number 250-010	NIMES Cedex 9	France	30029
32	Investigational Site Number 250-003	POITIERS Cedex	France	86021
33	Investigational Site Number 250-004	Toulouse Cedex 3	France	31076
34	Investigational Site Number 250-005	Valence Cedex 9	France	26953
35	Investigational Site Number 250-001	Vandoeuvre Les Nancy	France	54511
36	Investigational Site Number 276-003	Berlin	Germany	13055
37	Investigational Site Number 276-006	Bernau	Germany	16321
38	Investigational Site Number 276-001	Bonn	Germany	53115
39	Investigational Site Number 276-011	Dresden	Germany	01099
40	Investigational Site Number 276-010	Frankfurt am Main	Germany	60594
41	Investigational Site Number 276-002	Hamburg	Germany	22041
42	Investigational Site Number 276-008	Hamburg	Germany	22527
43	Investigational Site Number 276-009	Heidenau	Germany	01809
44	Investigational Site Number 276-004	Kiel	Germany	24105
45	Investigational Site Number 276-005	Ludwigsburg	Germany	71634
46	Investigational Site Number 276-007	Paderborn	Germany	33098
47	Investigational Site Number 376002	Ashkelon	Israel
48	Investigational Site Number 376001	Beer Yaakov	Israel
49	Investigational Site Number 380-005	Ancona	Italy	60100
50	Investigational Site Number 380-002	Barga	Italy	55051
51	Investigational Site Number 380-004	Catania	Italy	95124
52	Investigational Site Number 380-001	Como	Italy	22100
53	Investigational Site Number 380-006	Cortona	Italy	52042
54	Investigational Site Number 380-011	Mestre	Italy	30174
55	Investigational Site Number 380-010	Palermo	Italy	90127
56	Investigational Site Number 380-007	Roma	Italy	00168
57	Investigational Site Number 380-003	Roma	Italy	00169
58	Investigational Site Number 380-009	San Daniele Del Friuli	Italy	33038
59	Investigational Site Number 380-012	Varese	Italy	21100
60	Investigational Site Number 410001	Seoul	Korea, Republic of	152-703
61	Investigational Site Number 410002	Seoul	Korea, Republic of
62	Investigational Site Number 410003	Seoul	Korea, Republic of
63	Investigational Site Number 410004	Seoul	Korea, Republic of
64	Investigational Site Number 410005	Seoul	Korea, Republic of
65	Investigational Site Number 410006	Suwon	Korea, Republic of	443-721
66	Investigational Site Number 484017	Aguascalientes	Mexico	20230
67	Investigational Site Number 484012	Chihuahua	Mexico	31238
68	Investigational Site Number 484008	Guadalajara	Mexico	44200
69	Investigational Site Number 484009	Guadalajara	Mexico	44600
70	Investigational Site Number 484015	Guadalajara	Mexico	44600
71	Investigational Site Number 484002	Leon	Mexico	37150
72	Investigational Site Number 484016	Mexico	Mexico	06140
73	Investigational Site Number 484004	Mexico	Mexico	07760
74	Investigational Site Number 484005	Monterrey	Mexico	64460
75	Investigational Site Number 484003	Monterrey	Mexico	64710
76	Investigational Site Number 484001	Queretaro	Mexico	76000
77	Investigational Site Number 484013	Saltillo	Mexico	25230
78	Investigational Site Number 484011	Tijuana	Mexico	22450
79	Investigational Site Number 528003	Amsterdam	Netherlands
80	Investigational Site Number 528005	Goes	Netherlands
81	Investigational Site Number 528002	Groningen	Netherlands
82	Investigational Site Number 528001	Maastricht	Netherlands
83	Investigational Site Number 528004	Rotterdam	Netherlands
84	Investigational Site Number 620005	Amadora	Portugal	2720-276
85	Investigational Site Number 620001	Lisboa	Portugal	1169-024
86	Investigational Site Number 724004	El Palmar (MURCIA)	Spain	30120
87	Investigational Site Number 724005	Hospitalet de Llobregat	Spain	08907
88	Investigational Site Number 724008	La Coruña	Spain	15006
89	Investigational Site Number 724003	LLeida	Spain
90	Investigational Site Number 724010	Madrid	Spain	28034
91	Investigational Site Number 724001	Madrid	Spain	28040
92	Investigational Site Number 724002	Majadahonda	Spain	28222
93	Investigational Site Number 724006	Sevilla	Spain	41071
94	Investigational Site Number 724007	Tarragona	Spain	43007
95	Investigational Site Number 724009	Valencia	Spain	46014
96	Investigational Site Number 756001	Basel	Switzerland	4031
97	Investigational Site Number 756002	St.Gallen	Switzerland	9007
98	Investigational Site Number 158005	Kaohsiung Hsien,	Taiwan
99	Investigational Site Number 158006	Kaohsiung	Taiwan	807
100	Investigational Site Number 158009	Taichung City	Taiwan
101	Investigational Site Number 158004	Taichung	Taiwan	402
102	Investigational Site Number 158003	Taichung	Taiwan	407
103	Investigational Site Number 158002	Taipei	Taiwan	100
104	Investigational Site Number 158001	Taipei	Taiwan
105	Investigational Site Number 158008	Taipei	Taiwan
106	Investigational Site Number 158007	Tao Yuan Hsien	Taiwan
107	Investigational Site Number 826006	Belfast	United Kingdom	BT126BA
108	Investigational Site Number 826-005	Bournemouth	United Kingdom	BH77DW
109	Investigational Site Number 826-001	Carshalton	United Kingdom	SM51AA
110	Investigational Site Number 826-002	Gloucester	United Kingdom	GL13NN
111	Investigational Site Number 826-007	Wrexham	United Kingdom	LL137TD

Sponsors and Collaborators

Sanofi

Investigators

Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Sanofi

ClinicalTrials.gov Identifier:

NCT01140581

Other Study ID Numbers:

DRONE_C_03668
2009-016818-24

First Posted:

Jun 9, 2010

Last Update Posted:

Jan 23, 2012

Last Verified:

Jan 1, 2012

Additional relevant MeSH terms:

Atrial Fibrillation

Dronedarone

Study Results

No Results Posted as of Jan 23, 2012